Objective To investigate the mechanism and clinical significance of vincristine (VCR) inhibiting gastrinproliferation effects on human colon cell line SW480. Methods Effects of VCR on the viable cell count (A value), myoinositol triphosphate (IP3, CPM value), 〔Ca2+〕i and protein kinase C (PKC) activity of human colon cell line SW480 were evaluated in vitro by MTT assay,3Hmyoinositol incorporation, fluorescence measurements and γ-32P-ATP incorporation.Results A value of VCR+PG group was lower than that of PG or control group (Ｐ＜0.01 vs control, Ｐ＜0.01 vs PG). The concentration of IP3 or 〔Ca2+〕i in VCR+PG group was lower than that in PG group (Ｐ＜0.01 vs PG); and the PKC activity of membrane was lower than that in PG group (Ｐ＜0.05 vs PG, Ｐ＞0.05 vs control). Conclusion Effects of vincristine may be through the phosphoinositide signaling pathway on gastrinstimulating cell proliferation in human colon cell line SW480. It has provided an experimental evidence for antisignaling therapy for patients with colon cancer.